PROJECT SUMMARY Falls are the leading cause of fatal and non-fatal injuries among adults aged 65 and older. Medications that affect the central nervous system (i.e., CNS-active medications) are a key modifiable risk factor for falls, and national guidelines offer clear guidance on medications to avoid for those at risk of falls. However, healthcare provider and patient awareness of medications linked to falls is low, and to date the role of pharmacists in facilitating medication review and reduction to prevent falls has been limited. New approaches to increase uptake of recommendations are thus greatly needed. A multifaceted approach is often essential to successfully taper and discontinue certain CNS-active medications, such as benzodiazepines and opioids. The objective of STOP-FALLS is to implement and evaluate a team-based intervention involving pharmacists, primary care providers, and patients to reduce exposure to CNS-active medications that increase the risk of older adult falls and unintentional injuries. Central to our intervention is direct-to patient education and ongoing provider education and support. The aims are to: 1) ADAPT AND PILOT-TEST approaches necessary for adoption and implementation of evidence-based medication reduction strategies for use in an integrated health care system; 2) IMPLEMENT AND EVALUATE the intervention using an observational cohort design; and 3) ASSESS barriers and facilitators to intervention adoption, implementation and maintenance: clinical leadership influences, intervention adaptability, and implementation costs. Our intervention cohort will consist of older adults who are taking one or more CNS- active medications after the start of intervention implementation by the health system. We will compare this group with a recent historical comparison cohort from the same health plan using the same eligibility criteria for whom we have comparable data on demographics, medical and medication history, and outcomes. The primary outcome will be medically treated falls at 24 months. Secondary outcomes will be unintentional overdose, injuries due to motor vehicle crashes, and direct medical costs of the intervention. Our application is significant because pragmatic approaches to curtail unnecessary CNS- active medication use, by discontinuation of current use and preventing future use, will greatly enhance the capability of health systems to implement population-based fall and injury prevention. With a rapidly aging population and the devastating effects of unintentional injuries and their associated costs, such approaches are greatly needed. Such models could also improve the quality of prescribing more generally in older adults.